Candida albicans is an opportunistic pathogen and the most common fungus causing systemic infections in man including both bloodstream infections in hospital immunocompromised patients and vaginal infections (for review, see: Mandell, G. L.; Bennett, J. E.; and Dolin, R. (Eds), Principles and Practice of Infectious Disease, 4th ed., Churchill Livingston: New York, 1995; Vol 2, Chapter 237). The increasing use of immunosuppressive therapy for malignancy and transplantation, the increase of intensive care patients receiving broad spectrum antibiotic therapy, and the AIDS epidemic have greatly increased the number of patients susceptible to opportunistic infections caused by C. albicans. In particular, infections due to Candida increased by almost 500% over the decade of the 1980's and continue to rise in the 1990's, becoming the fourth most common blood-stream pathogen (see: Pfaller, M. A. Journal of Hospital Infection 30 suppl:329-38 (1995)). It has been reported that 90% of AIDS patients have some type of Candida infection. C. albicans can invade the kidneys, heart, liver, lungs, spleen, brain and eyes. These infections are difficult to detect and can lead to death.
A limited number of antifungal agents are available for the treatment for C. albicans infections. Amphotericin B, the mainstay of antifungal therapy, has limited clinical utility in treating Candida infection due to its associated toxicities and requirement for intravenous administration. Flucytosine too is limited due to its bone marrow toxicity and to the appearance of resistance. The azole antifungal agents have become the first choice of therapy for Candida infections, and fluconazole is the most frequent drug prescribed in the 1990's. However, reports of resistance to these azole antifungals have appeared in recent years (see: Dupont, B. Current Opinion in Infectious Diseases 8:424-427 (1995)). Because of the development of resistance to antifungals and adverse side-effects of current therapies for Candida infection, there is continuing need for new drug targets and new antibiotics.